In a variety of organs or tissues, fibrosis causes reduction of parenchyma cells therein and an increase of fibrous connective tissues, eventually damaging tissue structures, causing tissue dysfunction or even organ failure. The mechanism of fibrosis, and diagnostic methods and prevention measures for fibrosis of organs or tissues have been widely studied. In prior art, considerable progress has been made in some aspects, but some key unresolved issues still exist.
U.S. Pat. No. 3,839,346A, U.S. Pat. No. 4,052,509A, U.S. Pat. No. 4,042,699 disclose 29 pyridone compounds having structural formula I as follows,
and disclose functions of the pyridone compounds of resisting inflammation, allaying fever, reducing the level of serum uric acid, relieving pain or the like, wherein 5-methyl-1-phenyl-2(1H)-pyridone (Pirfenidone, PFD) has the best activity and lower toxicity.
U.S. Pat. No. 5,310,562 discloses 5-methyl-1-phenyl-2(1H)-pyridone for the first time in 1994, that is Pirfenidone (PFD), having an anti-fibrosis biological activity; subsequently U.S. Pat. Nos. 5,518,729 and 5,716,632 disclose N-substituted-2-(1H)pyridone described as the structural formula I and N-substituted-3-(1H)pyridone having the same anti-fibrosis function. Forty-four compounds are specified, most of which are known compounds derived from U.S. Pat. No. 4,052,509; and in the compounds, R1, R2, R3, and R4 are defined as methyl groups or ethyl groups.
Pirfenidone (PFD) is proven to have effectiveness in fibrosis prevention through in vitro and animal experiments. Pirfenidone has functions of stopping or even converting ECM accumulation and preventing or reversing fibrosis and scar formation in experiments using animals with renal fibrosis and pulmonary fibrosis and in the clinical treatment of patients with idiopathic pulmonary fibrosis (Shimizu T, Fukagawa M, Kuroda T, et al. Pirfenidone prevents collagen accumulation in the remnant kidney in rats with partial nephrectomy. Kidney Int, 1997, 52 (Suppl 63): S239-243; Raghu G, Johnson W C, Lockhart D, et al. Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone. Am J Respir Crit Care Med, 1999, 159: 1061-1069).
The applicant proposes a CN patent ZL02114190.8 and provides a class of pyridone compounds of the structural formula II.
In structural formula II, if n=1, the substituent R is F, Br, or I;if n=2, the substituents R are F, Cl, Br, I, a saturated linear alkyl group, an oxo-substituted saturated linear alkyl group, or a halo-substituted saturated linear alkyl group.
The substituent R is at any of the ortho-position, meta-position, and para-position on a benzene ring.
Pirfenidone has come into the market in Japan in 2008 for treating indications for pulmonary fibrosis. However, Pirfenidone and its derivatives do not have high enough strength. The clinical dose of Pirfenidone achieves 2400 mg/day.
Patent publications WO2007053685 and WO2006122154 disclose compounds having functions of inhibiting p38 kinase, applied to treatment of fibrosis diseases and disclose the structural formula III;
wherein, R1-R4 each are H, alkyl, substituted allyl, alkenyl, haloalkyl, nitroalkyl, hydroxyalkyl, alkoxyl, phenyl, substituted phenyl, halogen, hydroxyl, alkoxyalkyl, carboxyl, alkoxycarbonyl, etc.; X1-X5 each are H, halogen, an alkoxyl group, or a hydroxyl group.
WO2007062167 also discloses compounds having functions of inhibiting p38 kinase and applied to treatment of various fibrosis diseases, wherein some structures are shown as follows:

Some simple substituents are provided on the benzene rings of the compounds.
CN patent 200710034357 discloses some similar compounds having the above structures with anti-fibrosis activity and a compound with the anti-fibrosis activity shown in the structural formula IV.

Those compounds are provided with TFM at the 5-position of the pyridone ring without any substitutents on the aromatic ring of the phenyl group, thereby overcoming the disadvantages of inferior action of Pirfenidone.
DE patent DE4343528 reports a class of compounds having insecticidal actions for agricultural use, with the structural formula V as follows.
In structural formula V, A and B are substituted by various heterocyclic rings, such as furan, imidazole, pyridine and pyridone; wherein a class of compounds with the structural formula VI is included.

EP patents EP259048, EP367410 and EP398499 report a class of compounds having insecticidal actions for use in agriculture, with the structural formula VII as follows:
wherein a class of compounds having the structural formula VIII, in which R1 is pyridone and R10 is O or S, is included.

EP patent EP216541 reports a class of compounds having insecticidal actions for use in agriculture, with the structural formula IX as follows:
wherein a class of compounds with the structural formula X is included.

EP patent EP488220 reports a class of compounds having insecticidal actions, with the structural formula XI as follows:

In structures of the above-mentioned compounds, the pyridine ring and the benzene ring at the 1-position of the pyridine ring have a plurality of substituents; the compounds with complicated structures have not been reported to have the anti-fibrosis function. In the meanwhile, more fluorine atoms in the structure will result in stronger lipid solubility of the molecule.
DE102004027359 discloses a class of compounds capable of modulating dopamine-3 receptor activity and applied to treatment of Parkinson's disease and schizophrenosis;
wherein, A is a hydrocarbon chain with 4-6 atoms, having 1-2 substituted methyl groups thereon; or 1-2 carbon atoms in the carbon chain are substituted by O, C═O, S and other atoms; R1 and R2 are H, CN, NO2, a halogen atom, OR5, NR6R7, C(O)NR6R7, O—C(O)NR6R7; C1-C6 alkyl, C1-C6 haloalkyl, etc.